Pyridine or pyrimidine derivatives

Abstract

The present invention relates to compounds of formula I wherein R 1′ is methyl; R 1 is methyl, ethyl, CF 3 , CH 2 OH, cyclopropyl or cyano, or R 1′ and R 1 may form together a 1,1-dioxo-tetrahydro-thiophen-3-yl ring; R 2 is hydrogen, methyl, ethyl, isopropyl, tert-butyl, cyclopropyl, cyclopropylmethyl, or hydroxmethyl; R 3 is Cl, F, CF 3 , methyl, methoxy, or cyclopropyl; R 4 is hydrogen, methyl, F or Cl; X is N or CH; Y is N or CH; with the proviso that X and Y are not simultaneously CH; or to a pharmaceutically acceptable salt or acid addition salt, to a racemic mixture, or to its corresponding enantiomer and/or optical isomer and/or stereoisomer. The compounds of formula I may be used in the treatment of psychiatric disorders such as schizophrenia, bipolar disorder, obsessive-compulsive disorder or autism spectrum disorder.

The invention claimed is: 
     
       1. A compound of formula I: 
       
         
           
           
               
               
           
         
         wherein 
         R 1′  is methyl; 
         R 1  is methyl, ethyl, CF 3 , CH 2 OH, cyclopropyl or cyano, or R 1′  and R 1  may form together a 1,1-dioxo-tetrahydro-thiophen-3-yl ring; 
         R 2  is hydrogen, methyl, ethyl, isopropyl, tert-butyl, cyclopropyl, cyclopropylmethyl, or hydroxmethyl; 
         R 3  is Cl, F, CF 3 , methyl, methoxy, or cyclopropyl; 
         R 4  is hydrogen, methyl, F or Cl; 
         X is N or CH; 
         Y is N or CH;
 with the proviso that X and Y are not simultaneously CH; 
 
         or a pharmaceutically acceptable salt or acid addition salt, a racemic mixture, or its corresponding enantiomer and/or optical isomer and/or stereoisomer. 
       
     
     
       2. A compound of formula IA according to  claim 1 : 
       
         
           
           
               
               
           
         
         wherein 
         R 1″  is methyl; 
         R 1  is methyl, ethyl, CF 3 , CH 2 OH, cyclopropyl or cyano, or R 1′  and R 1  may form together a 1,1-dioxo-tetrahydro-thiophen-3-yl ring; 
         R 2  is hydrogen, methyl, ethyl, isopropyl, tert-butyl, cyclopropyl, cyclopropylmethyl, or hydroxmethyl; 
         R 3  is Cl, F, CF 3 , methyl, methoxy, or cyclopropyl; 
         R 4  is hydrogen, methyl, F or Cl; 
         or a pharmaceutically acceptable salt or acid addition salt, a racemic mixture, or its corresponding enantiomer and/or optical isomer and/or stereoisomer. 
       
     
     
       3. A compound of formula IA according to  claim 2 , or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of
 N-tert-Butyl-2-(4-chlorophenyl)-6-(4-propan-2-yl-pyrimidin-5-yl)-pyridine-4-carboxamide; 
 N-tert-Butyl-2-(4-fluorophenyl)-6-(4-propan-2-yl-pyrimidin-5-yl)-pyridine-4-carboxamide; 
 N-tert-Butyl-2-(4-propan-2-yl-pyrimidin-5-yl)-6-[4-(trifluoromethyl)-phenyl]-pyridine-4-carboxamide; 
 N-tert-Butyl-2-(4-methylphenyl)-6-(4-propan-2-yl-pyrimidin-5-yl)-pyridine-4-carboxamide; 
 N-tert-Butyl-2-(3,4-difluorophenyl)-6-(4-propan-2-yl-pyrimidin-5-yl)-pyridine-4-carboxamide; 
 N-tert-Butyl-2-(4-fluoro-3-methylphenyl)-6-(4-propan-2-yl-pyrimidin-5-yl)-pyridine-4-carboxamide; 
 N-tert-Butyl-2-(4-chloro-3-fluorophenyl)-6-(4-propan-2-yl-pyrimidin-5-yl)-pyridine-4-carboxamide; 
 N-tert-Butyl-2-(4-cyclopropyl-phenyl)-6-(4-propan-2-yl-pyrimidin-5-yl)-pyridine-4-carboxamide; 
 2-(4-Chlorophenyl)-N-(2-cyclopropyl-propan-2-yl)-6-(4-propan-2-yl-pyrimidin-5-yl)-pyridine-4-carboxamide; 
 2-(4-Chlorophenyl)-N-(2-cyanopropan-2-yl)-6-(4-propan-2-yl-pyrimidin-5-yl)-pyridine-4-carboxamide; 
 2-(4-Chlorophenyl)-N-(1-hydroxy-2-methylpropan-2-yl)-6-(4-propan-2-yl-pyrimidin-5-yl)-pyridine-4-carboxamide; 
 2-(4-Chlorophenyl)-6-(4-propan-2-yl-pyrimidin-5-yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)-pyridine-4-carboxamide; 
 N-tert-Butyl-2-(4-methoxyphenyl)-6-(4-propan-2-yl-pyrimidin-5-yl)-pyridine-4-carboxamide; 
 N-tert-Butyl-2-(3-fluoro-4-methylphenyl)-6-(4-propan-2-yl-pyrimidin-5-yl)-pyridine-4-carboxamide; 
 (RS)-2-(4-Fluorophenyl)-N-(3-methyl-1,1-dioxothiolan-3-yl)-6-(4-propan-2-yl-pyrimidin-5-yl)-pyridine-4-carb oxamide; 
 2-(4-Fluorophenyl)-N-(2-methylbutan-2-yl)-6-(4-propan-2-yl-pyrimidin-5-yl)-pyridine-4-carboxamide; 
 N-tert-Butyl-2-(4-ethyl-pyrimidin-5-yl)-6-(4-fluorophenyl)-pyridine-4-carboxamide; 
 N-tert-Butyl-2-(4-fluorophenyl)-6-(4-methylpyrimidin-5-yl)-pyridine-4-carboxamide; 
 N-tert-Butyl-2-(4-cyclopropylpyrimidin-5-yl)-6-(4-fluorophenyl)-pyridine-4-carboxamide; 
 N-tert-Butyl-2-(4-tert-butyl-pyrimidin-5-yl)-6-(4-fluorophenyl)-pyridine-4-carboxamide; 
 N-tert-Butyl-2-(4-tert-butylpyrimidin-5-yl)-6-(4-chlorophenyl)-pyridine-4-carboxamide; and 
 N-tert-Butyl-2-(4-tert-butyl-pyrimidin-5-yl)-6-[4-(trifluoromethyl)-phenyl]-pyridine-4-carboxamide. 
 
     
     
       4. A compound of formula IB according to  claim 1 : 
       
         
           
           
               
               
           
         
         wherein 
         R 1′  is methyl; 
         R 1  is methyl, ethyl, CF 3 , CH 2 OH, cyclopropyl or cyano, or R 1′  and R 1  may form together a 1,1-dioxo-tetrahydro-thiophen-3-yl ring; 
         R 2  is hydrogen, methyl, ethyl, isopropyl, tert-butyl, cyclopropyl, cyclopropylmethyl, or hydroxmethyl; 
         R 3  is Cl, F, CF 3 , methyl, methoxy, or cyclopropyl; 
         R 4  is hydrogen, methyl, F or Cl; 
         or a pharmaceutically acceptable salt or acid addition salt, a racemic mixture, or its corresponding enantiomer and/or optical isomer and/or stereoisomer. 
       
     
     
       5. A compound of formula IB according to  claim 4 , or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of
 N-tert-Butyl-2-(4-fluorophenyl)-6-(4-methylpyridin-3-yl)-pyridine-4-carboxamide; 
 N-tert-Butyl-2-(4-chlorophenyl)-6-(4-methylpyridin-3-yl)-pyridine-4-carboxamide; 
 N-tert-Butyl-2-(4-propan-2-yl-pyridin-3-yl)-6-[4-(trifluoromethyl)-phenyl]-pyridine-4-carboxamide; 
 N-tert-Butyl-2-(4-chlorophenyl)-6-(4-propan-2-yl-pyridin-3-yl)-pyridine-4-carboxamide; and 
 N-tert-Butyl-2-(4-fluorophenyl)-6-(4-propan-2-yl-pyridin-3-yl)-pyridine-4-carboxamide. 
 
     
     
       6. A process for the manufacture of a compound of formula I, or a pharmaceutically acceptable salt thereof, as defined in  claim 1 , which process comprises:
 a) reacting a compound of formula 
 
       
         
           
           
               
               
           
         
       
       with a compound of formula 
       
         
           
           
               
               
           
         
       
       to form a compound of formula I 
       
         
           
           
               
               
           
         
       
       or
 b) reacting a compound of formula 
 
       
         
           
           
               
               
           
         
       
       with a compound of formula 
       
         
           
           
               
               
           
         
       
       to form a compound of formula I 
       
         
           
           
               
               
           
         
       
     
     
       7. A pharmaceutical composition comprising a compound of formula I as claimed in  claim 1 , or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients. 
     
     
       8. A method for the treatment of schizophrenia, bipolar disorder, obsessive-compulsive disorder or autism spectrum disorder in a mammal, which method comprises administering an effective amount of a compound of formula I as claimed in  claim 1 , or a pharmaceutically acceptable salt thereof, to the mammal.